Health Related Quality of Life: The Impact of Psoriasis When Designing Tailored Treatment Plans

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2 Disclaimer This slide deck in its original and unaltered format is for educational purposes and is current as of October The content and views presented in this educational activity are those of the authors and do not necessarily reflect those of Creative Educational Concepts or the supporter. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and offlabel uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.

3 Usage Rights This slide deck is provided for educational purposes and slides may be used for personal, non-commercial presentations only as long as content and references remain the same. No part of this slide deck may be published or distributed in print or electronic format without prior written permission from Creative Educational Concepts.

4 Learning Objectives Appraise the impact of psoriatic disease on patient quality of life, work productivity, psychological comorbidities, and associated psychosocial effects. Explore the unique aspects of emerging biologic agents for psoriasis in terms of inflammatory targets, efficacy, safety, and effects on comorbid conditions. Recognizing the importance of patient quality of life and the impact on treatment decisions, use real-world, case-based scenarios to design individualized treatment plans for patients with psoriasis that address individual patient needs such as disease severity, treatment history, quality of life, and comorbidities.

5 Health Related Quality of Life: The Impact of Psoriasis When Designing Tailored Treatment Plans

6 Psoriasis: A Complex Systemic Disease Most common autoimmune disease 2% to 3% of the United States (U.S.) population (~7.5 million Americans) Chronic, inflammatory Epidermal hyperproliferation Keratinocytes proliferate at a higher rate compared to normal skin Clinically evident as raised, inflamed, scaly red skin lesions, cracking, itching Typically affects outside of the elbows, knees, and scalp, but can appear on any location

7 The Cost of Psoriatic Disease to the U.S. Healthcare System Total direct and indirect healthcare costs ~$11.25 billion annually (data from 2014) Work loss: ~60% of patients with psoriasis missed an average of 26 days of work a year Horn EJ, et al. J Am Acad Dermatol. 2007; Rachakonda TD, et al. J Am Acad Dermatol

8 Cutaneous Lesions Red, raised patches and plaques with distinct borders and silvery scale Typical areas: elbows, nails, knees, scalp, groin Auspitz s Sign (peel away scale and specks bleed) Flares with stress, infection, ETOH, winter, medications (beta blockers, calcium channel blockers, lithium, etc.)

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10 What Do We Also See? Dysregulated immune system Increased number of inflammatory cells in psoriatic lesions Localized and systemic inflammation

11 Comorbidities Metabolic syndrome: Truncal obesity, hypertension, diabetes, hyperlipidemia Psychological impact: Increased anxiety Increased depression Poor self-image Lack of self-confidence Suicidal ideation Sexual dysfunction

12 Impact on Quality of Life Physical Psychosocial Everyday Activity 72% suffer from itching 70% from physical irritation 59% from pain Social stigmatization 39% increased risk of depression 31% increased risk of anxiety 44% increased risk of suicidality >70% are angry, frustrated, embarrassed, and/or helpless 88% said psoriasis affects overall emotional well-being 82% said psoriasis interferes with their enjoyment of life 30% reported that psoriasis interferes with sexual activities Armstrong AW, et al. PLoS One. 2012;

13 Psoriasis is Associated with Increased Risks of Mortality, CVD, MI, Stroke, and DM 50% increased risk of mortality 1 Die years younger Increased risk of cardiovascular disease (CVD) 2 58% increased risk of major adverse cardiac events 3 57% increased risk of cardiovascular death 4 Increased risk of myocardial infarction (MI) 43% increased risk of stroke 5 62% increased risk of diabetes mellitus (DM) 2 1 Gelfand JM, et al. Arch Dermatol. 2007; 2 Neimann AL, et al. J Am Acad Dermatol. 2006; 3 Mehta NN, et al. Am J Med. 2011; 4 Ahlehoff O, et al. J Intern Med. 2011; 5 Gelfand JM, et al. J Invest Dermatol

14 Percent (%) Patients With Psoriasis Are at Increased Risk for Cardiometabolic Disorders Proportion of diseases in patients with psoriasis vs. control group P<.0001 Psoriasis (N=16,850) Control (N=48,677) 0 DM Hypertension CHD Obesity CHD=coronary heart disease Cohen AD, et al. Dermatology. 2008; Sommer DM, et al. Arch Dermatol Res. 2006; Armstrong EJ, et al. J Am Heart Assoc

15 Psoriasis and Atherosclerosis: Shared Inflammatory Mediators Psoriasis Inflammation From Endothelial Dysfunction to Atherosclerosis Skin Keratinocytes + Inflammatory Cells TNF- IFN- IFN- IL-1 IL-6 IL-7 Liver Adipose Tissue Skeletal muscle CRP Fibrinogen LDL-C Triglyceride Leptin Resistin MCP-1 Insulin resistance Common link:?? Increased activity of inflammatory mediators CRP=C-reactive protein; IFN=interferon; IL=interleukin; TNF=tumor necrosis factor; MCP-1=monocyte chemotactic protein-1 Future research: Can biologic psoriasis therapy affect cardiovascular comorbidities? Gisondi P, Girolomoni G. Semin Thromb Hemost

16 Treating Psoriasis Can It Treat Depression? Etanercept 1 N=618 55% reduction in depressive symptoms measured by BDI (P<.0001) 43% improvement in HAM-D (P=.0048) Ustekinumab 2 N=1, % improvement in HADS- Depression (P<.001) 13.9% improvement in HADS- Anxiety (P<.001) 76.2% improvement in DLQI (P<.001) BDI=Beck Depression Inventory; DLQI=Dermatology Life Quality Index; HADS=Hospital Anxiety and Depression Scale; HAM-D=Hamilton Rating Scale for Depression 1 Tyring S, et al. Lancet. 2006; 2 Langley RG, et al. J Am Acad Dermatol

17 The Million Dollar Question. Will treating psoriasis (and psoriatic arthritis) systemically decrease/improve the other comorbidities?

18 Psoriatic Arthritis (PsA) Psoriatic arthritis occurs in 6%-40% of patients with cutaneous psoriasis (dependent on the population studied) Joint symptoms can precede skin symptoms Joint symptoms on average develop 7-10 years after the original diagnosis Kimball AB, et al. J Am Acad Dermatol. 2008; Gelfand JM, et al. J Am Acad Dermatol. 2005;

19 Risk Factors for PsA Younger age at psoriasis onset Higher worst-ever BSA Koebner phenomenon Female sex Nail involvement Obesity BSA=body surface area Kimball AB, et al. J Am Acad Dermatol. 2008; Gelfand JM, et al. J Am Acad Dermatol. 2005;

20 PsA: Diagnosis There is no laboratory test used to definitively diagnose PsA No widely accepted classification or diagnostic criteria, but several clinical features help facilitate the diagnosis in these patients Diagnosis is based on history, physical examination, and/or radiographic features Conjunctivitis is a comorbidity of PsA (~1/5 of patients) Harrison BJ, et al. J Rheumatol. 1997; Mease P, Goffe BS. J Am Acad Dermatol. 2005; Gladman DD, et al. Arthritis Rheum. 2004; Lambert JR, Wright V. Ann Rheum Dis

21 Degrees of Plaque Psoriasis Severity Mild Moderate Severe Photographs reprinted with permission from National Psoriasis Foundation; immunology/presentations/group8/autoimmunity/psoriasis.htm.

22 Calculating BSA Psoriasis Coverage and Severity Disability or significant impact on quality of life Palm of patient s hand=1% of BSA Mild Less than 3% of the body Moderate 3%-10% of the body Severe More than 10% of the body Psoriasis involving the palms, genitalia, and soles may be severe Menter A, et al. J Am Acad Dermatol. 2008;

23 Not the Whole Picture Location Groin/genitalia Palms/soles of feet Symptoms Psychological impact Impairment of normal activities Work Relationships/social interaction Enjoyment of public places

24 Patients With Marked or Severe Psoriasis (%) Do We Underestimate the Impact of Psoriasis on Patients Lives? Physician and Patient Global Assessments of Psoriasis Severity at Baseline: Percentage of Patients With Marked or Severe Psoriasis 80 75% % 0 Physician Assessment Patient Self-Assessment Leonardi CL, et al. N Engl J Med

25 So How Do You Get a Sense of Patient Perception? Koo-Mentor instrument? My approach: Open-ended questions Questions: Symptoms does your skin itch, sting, burn,or hurt? How much does your psoriasis bother you? Is there anything you do or do NOT do because of your psoriasis? Does your skin make you feel depressed? I am supposed to rate your psoriasis as mild, moderate, or severe. How would you classify it? Besides a cure, which I do not have, what do you wish I had to give you as a treatment today? Any audience pearls to ask?

26 Patients Want More Aggressive Therapy National Psoriasis Foundation (NPF) Telephone Survey Respondents With Severe Psoriasis (%) Frustrated With Ineffective Therapies 78% Treatments Not Aggressive Enough 32% Physicians Could Be More Helpful 59% Percent of Patients (N=502) Krueger G, et al. Arch Dermatol

27 Examining Emerging Biologic Agents in Practice: Efficacy, Safety, and the Role of Comorbid Conditions

28 Treatment Guidelines Psoriasis +/- psoriatic arthritis Anti-TNF +/- MTX YES NO Limited disease Extensive disease Topicals/Targeted phototherapy UVB/PUVA Systemic Biologic MTX=methotrexate Lack of Effect Menter A, et al. J Am Acad Dermatol

29 Percent of Patients A Majority of Patients with Moderate-to-Severe Psoriasis are Undertreated NPF Survey, (N=5,604) Psoriasis Not Receiving Guideline-Recommended Treatment Untreated Moderate 30% 36% Severe 22% 30% 80% 70% 60% 50% 40% 30% 20% 10% 0% NPF Survey, 2007 (N=1,657) 71% 73% 57% 22% 11% 12% 6% 7% 11% 15% 9% 7% Mild (<3% BSA) Moderate (3%-10% BSA) Severe (>10% BSA) Topical therapy (topical only) Phototherapy (mono or combined with topical) Traditional systemic therapy (mono or combined with photo or topical) Biologic therapy (mono or combined with systemic, photo or topical) Armstrong AW, et al. JAMA Dermatol. 2013; Horn EJ, et al. J Am Acad Dermatol

30 My Treatment Guidelines PSA=systemic therapy Mild psoriasis =topicals Moderate to severe Complex discussion based on patient s perception of severity, quality of life, comorbidities, previously tried therapies, and risk/benefit discussion The insurance carrier s guidelines

31 Mild Cutaneous Disease Topical steroids Topical vitamin D derivatives Topical vitamin A derivatives Tar based products Excimer laser therapy Injected steroids **THE most important part of treatment counseling on comorbidities

32 Specific Examples Triamcinolone Ointment 0.1% twice daily 3 weeks on, 3 weeks off Clobetasol ointment to body plaques only alternate with calcipotriene topical cream Scalp: clobetasol foam three times a week, tar based shampoo daily Face/groin: Desonide ointment alternating with calcipotriene **Rotate topical steroids to avoid side effects Give steroid sparing agents to fill in the gaps and treat/prevent particular lesions

33 Side Effects of Steroids Skin thinning Changes in pigmentation Easy bruising Stretch marks Redness and dilated surface blood vessels Steroid induced rosacea Dependency and rebound Systemic absorption

34 Oral or Injected Steroids Oral Steroids IM injections Joint injections

35 Moderate to Severe Psoriasis Light therapy: Narrow band UVB therapy or UVA therapy Traditional systemic therapy: Methotrexate, Cyclosporine, Acitretin Biologics: Adalimumab Etanercept Infliximab Secukinumab Ustekinumab Not a biologic: Apremilast (oral)

36 Conventional Systemic Therapy Agent Adverse Event Contraindications Considerations Methotrexate Cyclosporine Acitretin Hepatotoxicity, drug interactions, immunosuppression, bone marrow suppression, pneumonitis, birth defects, decreased sperm count, miscarriage Immunosuppression, impaired renal function, hypertension, malignancies, drug interactions Birth defects, mucocutaneous effects, dyslipidemia Pregnancy a, breastfeeding, renal impairment, hepatitis, cirrhosis, leukopenia, thrombocytopenia, regular alcohol use, unreliability in patients Acute infections, active malignancies, uncontrolled hypertension, impaired renal function Pregnancy b, breastfeeding risk of hepatotoxicity with alcohol; females of childbearing potential or those who have liver disease are not good candidates Potential for levels with alcohol; potential for gout exacerbation Significant risk of increased cholesterol, particularly triglycerides; females of childbearing age are not good candidates a Rule out pregnancy in women of childbearing potential; avoid pregnancy if either partner is receiving methotrexate; contraception: women, during therapy and at least 1 ovulatory cycle afterward; men, at least 3 months after therapy. b Patients should not become pregnant for at least 3 years following drug discontinuation. Menter A, et al. J Am Acad Dermatol

37 What are Biologics? According to the FDA: cutting-edge of biomedical research and, in time, may offer the most effective means to treat a variety of medical illnesses and conditions that presently have no other treatments available Complex mixtures Tend to be heat sensitive and susceptible to microbial contamination - $$$

38 Biologic Agents for Psoriasis Drug Inflammatory Target First Generation Biologics Second Generation Biologics Third Generation Biologics Future Therapies Alefacept Efalizumab Adalimumab Etanercept Infliximab Secukinumab Ustekinumab Brodalumab Ixekizumab Tildrakizumab Tofacitinib T-cell TNF-α IL-17 IL-12/-23 IL-17 IL-23 JAK And more to come.

39 FDA Approved Biologics Agent Adalimumab (Humira ) Etanercept (Enbrel ) Infliximab (Remicade ) Secukinumab (Cosentyx ) Ustekinumab (Stelara ) Dosing 80 mg subcutaneously, followed by 40 mg subcutaneously every other week 50 mg subcutaneously twice weekly for 12 weeks, then 50 mg subcutaneously each week 5 mg/kg IV at weeks 0, 2, 6, then every 8 weeks 300 mg subcutaneously weekly for 4 weeks, followed by 300 mg subcutaneously every 4 weeks 45 mg subcutaneously initially and 4 weeks later, followed by 45 mg every 12 weeks FDA Prescribing Information.

40 PASI 75 Response (% of Patients) Methotrexate Efficacy vs. Adalimumab Placebo Methotrexate Adalimumab * * 76.9% 79.6% * 62% # 35.5% 23.1% 24.5% 18.9% 13.2% 15.1% 9.1% 3.8% 2.7% Week 4 Week 8 Week 12 Week 16 # P=.001 adalimumab vs. placebo; *P<.001 adalimumab vs. placebo P<.001 adalimumab vs. methotrexate. Note: ITT: pts with missing PASI scores considered non-responders PASI=Psoriasis Area and Severity Index Saurat JH, et al. Br J Dermatol

41 Systemic Therapies: Biologics TNF-α Blockers Adalimumab Etanercept Infliximab IL-12/-23 Inhibitor Ustekinumab IL-17A Secukinumab Studies Common AEs a Black Box 3 major trials assessing efficacy After 16 weeks, approximately 80% of patients experienced a PASI 75 response >10 years of clinical data for this drug 3 major trials assessing efficacy After maintenance phase, patients remained at PASI 75 Two phase III clinical trials 33% of patients achieved a PASI 75 response after 12 weeks of treatment Two phase III clinical trials Demonstrated superiority to etanercept and ustekimumab a See package inserts for complete information on AEs. TB=tuberculosis; ANA=anti-nuclear antibody Injection site reaction, +ANA, elevated alkaline phosphatase, cholesterol Injection site reaction, +ANA Infusion reactions, +ANA, elevated LFT values, neutralizing antibodies Nasopharyngitis Headache, nasopharyngitis, diarrhea, fatigue, arthralgia Infection (TB, sepsis, fungal, opportunistic), malignancies Infection (TB, sepsis, fungal, opportunistic), malignancies Infection (TB, sepsis, fungal, opportunistic), hepatosplenic T-cell lymphoma None None Kupetsky E, et al. J Am Board Fam Med. 2013; Thaci D, et al. J Am Acad Dermatol

42 PASI 75, Mean % of Patients PASI Estimated Probabilities of Response 80 For the majority of trials, the double-blind period was of 12 weeks duration (range weeks) The positions of ustekinumab 45 mg and ustekinumab 90 mg are reversed when the ustekinumab data are analyzed according to the dosing recommendations listed in the Summary of Product Characteristics (eg, 45 mg in patients <100 kg and 90 mg in patients >100 kg). Reich K, et al. Br J Dermatol

43 Patients with Response (%) Secukinumab Phase III Psoriasis Results PASI 75 Response Through 52 Weeks ERASURE FIXTURE * Secukinumab 300 mg (N=245) * Secukinumab 300 mg N= * Placebo (N=247) Secukinumab 150 mg (N=245) * Etanercept (N=323) Placebo (N=324) Secukinumab 150 mg (N=327) Week Week Secukinumab 150 mg Secukinumab 300 mg Etanercept Placebo *P<.001 for each secukinumab dose vs. comparators Langley RG, et al. N Engl J Med

44 Long-Term Safety Data for Biologics TNF inhibitors Upper respiratory tract infections Heart failure and lymphoma Avoid in patients with demyelinating disorders Adalimumab Infections were most frequent AE, consistent with previous analyses Overall malignancy rates did not differ from the general population Etanercept Low rates of serious infectious events and lymphoma Infrequent TB reactivation Infliximab Avoid intermittent therapy due to the higher incidence of serious infusion-related reactions and serious infections in this group *Lower samples size, shorter duration in studies Burmester GR, et al. Ann Rheum Dis. 2013; Papp KA, et al. Br J Dermatol. 2013; Mansouri Y, Goldenberg G. J Clin Aesthet Dermatol

45 Long-Term Safety Data for Biologics IL-12/-23 inhibitor No dose-related or cumulative toxicity was observed with increasing duration of ustekinumab exposure for up to 5 years Rates of AEs reported in ustekinumab psoriasis trials are comparable with those reported for other biologics approved for the treatment of patients with moderate-to-severe psoriasis Burmester GR, et al. Ann Rheum Dis. 2013; Papp KA, et al. Br J Dermatol

46 Monitoring for Biologics Initial assessment of immunization status or disease history: Haemophilus influenzae Tetanus Pertussis Varicella zoster Hepatitis A and B Human papillomavirus Streptococcus pneumoniae Lebwohl M, et al. J Am Acad Dermatol. 2008; Wine-Lee L, et al. J Am Acad Dermatol. 2013; FDA Prescribing Information. TNF-α blockers (adalimumab, etanercept, infliximab) and ustekinumab Complete blood cell count + platelets: baseline and every 2-6 months Chemistry screen + LFT: baseline and every 3-4 months TB skin test: baseline and annually thereafter Discussion about pregnancy Hepatitis and HIV screening in patients at risk

47 Hepatitis B Screening Patients with psoriasis who are candidates for TNF- inhibitor: Undergo screening for hepatitis B virus infection using the triple serology: Hepatitis B surface antigen Hepatitis B surface antibody Hepatitis B core antibody Advisable that patients who are candidates for ustekinumab, cyclosporine, or MTX undergo same screening Motaparthi K, et al. J Am Acad Dermatol

48 Vaccinations for Patients on Systemic Therapy Live vaccines are not recommended for patients taking MTX and contraindicated in patients taking cyclosporine and TNF-α inhibitors Patients taking ustekinumab should be considered immunosuppressed and vaccinated accordingly Inactive vaccines are safe, but therapeutic response may be reduced If a live vaccine is indicated, it should be given 4 weeks before initiation of therapy Patients should receive yearly influenza vaccine (inactivated) Routine immunizations should be up to date before travel Consultation with a travel medicine specialist should be sought 6 weeks before travel

49 What to Know for Primary Care No live vaccines Stop for infection (and talk with prescriber) Considerations for surgery Not meant to stop and start Annual TB test Regular lab monitoring Open dialog with prescriber of the medication

50 Apremilast Novel small molecule that blocks PDE4 in immune cells Oral, twice daily dosing Side effects Nausea/GI upset/diarrhea Depression Weight loss Safety No TB reactivation No lab monitoring Pregnancy category C Efficacy

51 Patients Achieving PASI 75 (%) Apremilast Phase III (ESTEEM 1): PASI 75 by Prior Treatment Experience at Week % 33.1%* N= Overall No Prior Systemic No Prior Biologic Prior Biologic *P<.0001; P=.0273 vs. placebo. Conventional +/or biologics. LOCF, Full Analysis Set (N=844) 7.6% 38.7%* 5.9% DLQI Response in Patients with baseline score >5: Placebo (N=236)=34%; Apremilast (N=459)=70% 35.8%* 3.8% 26.5%* Placebo Apremilast 30 mg BID 0% 26.9% Failed Prior TNF Reich K, et al. Presented at AAD Annual Meeting; 2013; Papp K, et al. J Am Acad Dermatol

52 Apremilast Phase III (ESTEEM 1): AEs in 5% of Any Treatment (Weeks 0-16) Adverse Event (AE) N (%) Placebo (N=282) Apremilast 30 mg BID (N=560) Diarrhea* 20(7.1) 105(18.8) Nausea 19(6.7) 88(15.7) URTI 21(7.4) 57(10.2) Nasopharyngitis 23(8.2) 41(7.3) Tension headache 12(4.3) 41(7.3) Headache 13(4.6) 31(5.5) >96% of patients had mild/moderate or no AEs. 1 (0.4%) placebo and 2 (0.4%) apremilast 30 mg twice daily patients reported severe diarrhea or nausea. *Diarrhea includes loose stools and increased urgency. URTI=upper respiratory tract infection Papp K, et al. J Am Acad Dermatol

53 What s on the Horizon? Long term safety data Data that shows an improvement in other end points if treating systemically Even more specific and targeted therapy Agents with less overall potential for immune suppression

54 Percent Improvement in PASI Score Brodalumab: Phase II Efficacy Results Percent Improvement in PASI Scores over Time Week All P<.001 vs. placebo and vs. 70 mg dose of brodalumab P<.001 vs. placebo 210 mg Brodalumab group 140 mg Brodalumab group 280 mg Brodalumab group 70 mg Brodalumab group Placebo group The P value for the comparison of the 70 mg dose of brodalumab with placebo (P<.001) is for all the time points except week 2, for which the P value was.002. PASI denotes psoriasis-area-and-severity index. Not FDA approved for psoriasis, currently in clinical trials. Papp KA, et al. N Engl J Med

55 Patients with PASI 75(%) Ixekizumab: Phase III Efficacy Results Proportion of Patients Achieving PASI 75 From Baseline To Week Uncover-2 Ixekizumab every 2 weeks (N=351) Ixekizumab every 4 weeks (N=347) Etanercept (N=358) Placebo (N=168) 90% 78% 42% 2% Weeks Not FDA approved for psoriasis, currently in clinical trials Uncover-3 Ixekizumab every 2 weeks (N=385) Ixekizumab every 4 weeks (N=386) Etanercept (N=382) Placebo (N=193) 53% 7% Weeks 87% 84% Griffiths CE, et al. Lancet

56 % Patients Tildrakizumab: Phase IIb Psoriasis Trial PASI 75 at 16 Weeks PBO 5 mg 25 mg 100 mg 200 mg N=45 N=42 N=90 N=89 N=86 Note: ITT-NRI analysis; *P.001 vs. placebo * DLQI Mean Change from Baseline 5 mg=-4.9, 25 mg=-9.2, 100 mg=-8.5, 200 mg=-8.8, placebo=+1.0 * * * Targets IL-23, currently in Phase III trials Not FDA approved for psoriasis at this time PASI 90 at 16 Weeks 12.5 * PBO 5 mg 25 mg 100 mg 200 mg N=45 N=42 N=90 N=89 N=86 Papp K, et al. Br J Dermatol * *

57 Proportion of Patients Achieving PASI 75 Response (%) Tofacitinib: Phase III Efficacy Data 0 Oral Janus Kinase (JAK) Inhibitor, recent FDA filing seeking an indication for psoriasis 4 weeks: P< mg vs. etanercept weeks: P= mg vs. etanercept 6 Weeks 8 Tofacitinib 10 mg twice daily Etanercept 50 mg twice weekly Tofacitinib 5 mg twice daily Placebo Tofacitinib 10 mg twice daily was non-inferior to etanercept and superior to placebo at 12 weeks, and response was significantly larger than etanercept at 4 and 8 weeks. Bachelez H, et al. Lancet Percent of patients achieving 5 point DLQI reduction (in patients with DLQI 5 at baseline): Tofacitinib 5 mg=66.3%; Tofacitinib 10 mg=78.2%; Etanercept 50 mg=74.7; Placebo=31.8% 12 P<.0001 vs. placebo

58 Emerging Agents: Adverse Events Variable No. AEs (%) No. Serious AEs (%) Most Common AEs Brodalumab 1 (N=181) 138 (76) 9 (5) Nasopharyngitis, upper respiratory infection, arthralgia, Placebo (N=33) 33 (100) 6 (18) back pain, sinusitus Ixekizumab 2 (N=1,463) 843 (58) 28 (2) Nasopharyngitis, upper respiratory infection, injection Placebo (360) 160 (44) 7(2) site reaction, arthralgia, headache Tildrakizumab 3 (N=308) 76 (25) 4 (1) Placebo (N=45) 10 (22) 0 (0) Tofacitinib 4 (N=659) 378 (57) 12 (2) Placebo (N=107) 55 (51) 2 (2) Nasopharyngitis, headache Nasopharyngeal and upper respiratory tract infections, diarrhea, increases in cholesterol and creatine phosphokinase 1 Papp K, et al. J Am Acad Dermatol. 2014; 2 Griffiths CE, et al. Lancet. 2015; 3 Papp K, et al. Br J Dermatol. 2015; 4 Bachelez H, et al. Lancet

59 Take Home Points Psoriasis is a chronic multi-system disease Multiple associated comorbidities that require patient education, monitoring, and management Our patients may be suffering in silence Patients need appropriate referral to a dermatology provider who regularly manages many patients on systemic therapies These patients need co-management between the specialist and the primary care provider

60 Patient Cases

61 Patient: Mike 45 year old male patient with a known history of psoriasis since the age of 22 reports because his psoriasis has been flaring the past six months BP: 138/89 mmhg 235 lbs, 6 feet, BMI=31.9 kg/m 2, 2 healthy children, computer programmer Medications: metoprolol, metformin, men s one a day multi-vitamin, glucosamine chondroitin Previous treatments: light therapy (mild response), triamcinolone and hydrocortisone 2.5%, OTC tar, t-gel

62 Patient: Mike BSA: 6% BSA on arms, legs, back, abdomen No joint involvement What else do you want to know? Treatment options?

63 Patient: Carla 32 year old female presents to discuss treatment options for her psoriasis. She is working at a law firm and feel self conscious with clients and partners She previously did well for a year on adalimumab but discontinued because she moved here for a new job No joint involvement 3% BSA on hands, knees, elbows, scalp Medications: Triphasic norgestimate/ ethinyl estradiol, sertraline, Preparation H prn What else do you want to know?

64 Patient: Carla

65 Pregnancy Information for Selected Therapies Drug Topical steroids Vitamin D derivatives Vitamin A derivatives Methotrexate Cyclosporine Acitretin Adalimumab Etanercept Infliximab Secukinumab Ustekinumab Pregnancy Category C C X X C X B B B B B See package inserts for complete information on use in pregnancy. FDA Prescribing Information.

66 Patient: Carla Treatment options and considerations

67